PB2281: TRIAL IN PROGRESS: FOLLICULAR LYMPHOMA OUTCOMES IN RELAPSED/REFRACTORY PATIENTS TREATED WITH SYSTEMIC THERAPY IN A REAL-WORLD ASSESSMENT (FLORA)
Authors: Gandhi Laurent Damaj, Emmanuel Bachy, Qiufei MA, Christian Hampp, James Harnett, Rachel E Sobel, Jessica J Jalbert, Ruben Gw Quek, Wenhui Wei, Ning Wu, Vera Mastey, Joy Wang, Anit Bajwa, Benedikt Maissenhaelter, Chantal van Gils, Shivani Aggarwal, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Catherine Thieblemont
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. Despite effectiveness of first-line chemoimmunotherapy, relapses occur in most patients and remissions shorten with each recurrence. No well-defined standard of care exists for relapsed/refractory (R/R) FL. There is a substantial need to identify new approaches that offer innovative options for high-risk patients, can overcome disease resistance, avoid cumulative toxicity, reduce transformation risk, and raise the prospect of cure. Large-scale, patient-level, real-world (RW) evidence studies can provide a good understanding of outcomes with currently available therapies in routine clinical practice and contextualize results from uncontrolled, single arm clinical trials. Aims: The FLORA study aims to characterize RW treatment patterns and outcomes in a large cohort of ~450 adult patients with Grade 1–3a R/R FL from over 30 clinical sites in 12 countries across North America, Europe, and Asia. Among them, an analytic cohort will be created of ~165 patients who have measurable disease at baseline and PET/CT scans during follow-up, unless they died. Methods: FLORA (NCT05338879) is an electronic medical record-based observational, retrospective cohort study of patients with R/R FL who have received ≥2 prior lines of systemic therapy including an anti-CD20 antibody and an alkylator. The study population will be selected based on similar eligibility criteria as the FL Grade 1–3a arm of the odronextamab ELM-2 trial (NCT03888105; Figure). Patients must have measurable disease and have initiated ≥1 additional line of systemic therapy (salvage therapy) between Jan 01, 2015 and Dec 31, 2020 (indexing period) after meeting the criteria for R/R FL Grade 1–3a. FLORA will contextualize outcomes from patients with R/R FL enrolled in contemporaneous single-arm studies. To estimate RW objective response rate (ORR) by independent central review (ICR), analytical cohorts will be created from the FLORA population based on data requirements and matching feasibility. Patients will be propensity score matched and/or weighted to each patient in the ELM-2 trial (anticipated cohort, n=128). To identify prognostic variables for inclusion in the propensity score model, a systematic literature review was conducted (PROSPERO CRD42022307561) and findings were ranked by three key opinion leaders. The most important prognostic variables identified included progression of disease within 24 months, chemoimmunoresistance, refractory to last line of therapy, number of prior treatment lines, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, FL International Prognostic Index, age, and Ann Arbor Stage. Results: The primary endpoint of FLORA is ICR-assessed ORR (Lugano classification). Secondary endpoints include physician-assessed ORR as well as complete response rate, progression-free survival, duration of response, and disease control rate assessed by ICR and treating physician. Time to next treatment, overall survival, and histological transformation will also be evaluated. Subgroups of interest will include historical (Jan 01, 2015 to Nov 12, 2019) versus contemporary treatment (Nov 13, 2019 to Dec 31, 2020) and geographic region. Sensitivity analyses will be conducted in expanded cohorts to assess the impact of eligibility criteria and availability of scans. Summary/Conclusion: When complete, FLORA will provide important current information on the RW outcomes of patients with FL and provide a valuable source of control data for comparative studies in R/R FL.Keywords: Follicular lymphoma, Non-Hodgkin’s lymphoma, Relapsed lymphoma, Real world data